This research will examine behavioral and neurochemical changes accompanying chronic administration of high levels of manganese to mice. A comparison will be made of drug-induced changes in motor behaviors (e.g., drug-induced tremors, rigidity, motor activity) between normal mice and mice maintained on a diet containing high concentrations of manganese or injected with an organic manganese-containing compound. These effects, which may serve as indices of the toxicity to manganese, and which may be related to the clinical manifestations of the toxicity as well as other neurological diseases, will be monitored for various periods of time in mice of different ages. In addition, an attempt will be made to correlate the pharmacological changes with changes in the concentration and metabolism of the neurotransmitters dopamine and GABA in different parts of the brain as well as with the accumulation of manganese in blood and brain. It is hoped that these results will serve as a model for manganese toxicity for investigating the characteristics of neuronal changes occurring with long-term exposure to this metal and for gaining insight into the interrelationships in the function of the basal ganglia.